Cell Biochem Biophys (2015) 71:1051–1057 DOI 10.1007/s12013-014-0308-7
ORIGINAL PAPER
Prevalence and Risk Factors for Farmer’s Lung in Greenhouse Farmers: An Epidemiological Study of 5,880 Farmers from Northeast China Shuo Liu • Donghong Chen • Shuang Fu • Yangang Ren • Lingling Wang • Yibing Zhang Mingjing Zhao • Xiaoyu He • Xiaoge Wang
•
Published online: 26 October 2014 Ó Springer Science+Business Media New York 2014
Abstract The objectives of this epidemiological study were to evaluate the prevalence of farmer’s lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse,
ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m2 but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced. Keywords Farmer’s lung disease Greenhouse Prevalence
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s12013-014-0308-7) contains supplementary material, which is available to authorized users. S. Liu D. Chen L. Wang M. Zhao X. He X. Wang (&) Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, 4 East Chongshan Road, Shenyang 110032, Liaoning, People’s Republic of China e-mail: [email protected] S. Fu Department of Respiratory Medicine, The General Hospital of Fushun Mining Affairs Bureau, Fushun 113008, Liaoning, People’s Republic of China Y. Ren The Editorial Office, Chinese Journal of Practical Internal Medicine, Shenyang 110001, Liaoning, People’s Republic of China Y. Zhang Department of Scientific Research, The General Hospital of Shenyang Military Command, Shenyang 110015, Liaoning, People’s Republic of China
Farmer’s lung disease (FLD), the most prevalent form of occupational hypersensitivity pneumonitis (HP), is an important source of respiratory morbidity among farmers caused by chronic inhalation of microorganisms from moldy hay, straw, or grain [1]. These microorganisms are mainly composed of Thermophilic actinomyces, such as Saccharopolyspora rectivirgula (SR) or Thermoactinomyces vulgaris (TV) that grow in hay under the conditions of high temperature and high humidity [2, 3]. Clinically, FLD is generally characterized by influenza-like and respiratory symptoms, including dyspnea, cough, lassitude, headaches, nausea, occasional fever, and night sweating [4, 5]. It is estimated that the prevalence of FLD in farming populations range from 0.5 to 4.4 %, depending on various regions, climate, and seasons as well as differences in diagnostic methods and farming practices [1, 4]. In particular, FLD has been reported to be more common in the Northern latitudes and among diary farmers [1].
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China is still an agricultural country with approximately 360 million farmers consisting half of its labor force. To our knowledge, however, epidemiological studies have seldom been performed in Chinese farmers to evaluate the prevalence of FLD or to explore the potential risk factors for FLD. Plastic film greenhouse is a horticultural and agricultural facility with efficient energy conservation that provides the owner with an opportunity to grow plants year-round in a controlled environment. Over the years, due to demand of off-season vegetables and export of cut flowers, plastic film greenhouse has gained its popularity in Middle and North China since 1980 s. In recent years, more and more greenhouse farmers were diagnosed with FLD in our clinical practice. Therefore, this prompts us to conduct an epidemiological study to estimate the prevalence and to explore the potential risk factors for FLD among Chinese greenhouse farmers, which may provide insight into exposures associated with FLD, as well as ways to reduce exposure and allow individuals to return to their farming activities. To this end, we performed a screening survey between August 2006 and June 2009 on FLD in active and exclusive greenhouse farmers in four different regions of Liaoning Province.
Methods Plastic Film Greenhouses and Subjects A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of the four cities of Liaoning Province (Shenyang, Xinmin, Chaoyang, and Jinzhou). The characteristics of these greenhouses were measured and summarized in Table 1, including the height, inside temperature, relative humidity, ventilation frequency, sunlight duration, pesticide usage as well as the temperature, relative humidity, pH value and microorganisms of both surface and near-surface soil (10 cm layer). Farmers meeting any of the following criteria were excluded: (a) prior chronic respiratory diseases when working as a greenhouse farmer, such as chronic bronchitis, tuberculosis, bronchiectasis, bronchial asthma, intrathoracic sarcoidosis, or interstitial lung disease; (b) prior allergy-driven lung disease or organic dust toxic syndrome when working as a greenhouse farmer; (c) any one refuses or is not considered safe to undergo pulmonary ventilation function test such as with mental disorder, severe cardiovascular and cerebrovascular diseases, or surgical operation in the preceding 12 months; (d) refuses to answer the questionnaire or answers the items less than one-third of the questionnaire; (e) unable to measure the
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characteristics of the greenhouses. Out of the 5,880 invited subjects, 5,420 gave their informed consent and answered the questionnaire in full (response rate, 92.18 %); consisting of 2,660 men (2,660/5,420, 49.08 %) and 2,720 women (2,760/5,420, 50.92 %) with a mean age of 44.76 ± 10.66 years (range 22–74 years). The detailed characteristics of these farmers are shown in Table 2. The current study was approved by the regional ethics committee. Questionnaire A questionnaire with 99 items on age, gender, smoking habits, medical history, respiratory symptoms, and occupation details was used. All the questionnaires were filled out by several well-trained respiratory physicians through face-to-face interactions with the subjects. Measurements The pulmonary ventilation function of all participants was measured using a REF 910520 spirotel (Roma, Italy). Approximately 10–15 % of greenhouse farmers with FLD symptoms and 5 % of healthy farmers were asked to undergo additional clinical evaluations, including blood routine examination, blood gas analysis, sputum eosinophil count, routine chest X-ray, and measurement of serum precipitating antibody. The diagnosis of chronic obstructive pulmonary disease (COPD) and asthma was based on the conventional diagnostic criteria as previously described [6, 7]. Statistical Analysis All data were analyzed using the SPSS 11.5 statistical software package (SPSS, Inc., Chicago, IL, USA). Comparisons of prevalence rates were assessed by v2 test. The risk factors were evaluated by odds ratios and 95 % confidence interval (95 % CI) with a logistic regression model. A P value equal to or less than 0.05 was reported as statistically significant.
Results Prevalence of FLD in Greenhouse Farmers Out of the 5,880 invited subjects, 5,420 gave their informed consent and answered the questionnaire in full (response rate, 92.18 %). Of these 5,420 greenhouse farmers, 5.7 % (308/5,420) were diagnosed with FLD. According to the criteria described in Methods, 62.34 % (192/308) and 37.66 % (116/308) of them were further defined as severe
Cell Biochem Biophys (2015) 71:1051–1057 Table 1 Greenhouse characteristics
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Greenhouse variables
Vegetable cultivation
Poultry farming
Mushroom cultivation
Flower cultivation
Total (n)
334
126
167
208
\ 1.8 m
65
40
138
179
[ 1.8 m
269
86
29
29
Spring
28
14
23
15
Winter
28
23
24
22
Autumn
23
15
23
13
Spring
68
67
83
67
Winter Autumn
67 65
68 67
82 83
66 63
Spring
27
15
22
14
Winter
26
23
23
20
Autumn
23
14
20
12
11
12
11
11
Height (n)
Inside air temperature (°C)
Inside humidity (%)
Temperature of surface soil (°C)
Sunlight duration per day (h) Spring Winter
8
12
8
8
Autumn
10
12
10
11
Near-surface soil
a
The near-surface soil in poultry farming greenhouse is not available because of cement mortar protective course
b
Disinfectant, but not pesticide, is used in poultry farming greenhouse
Temperature (°C)
17
a
18
15
Humidity (%)
74
a
80
70
pH value
7.1
a
7.3
6.8
Microorganisms
Actinomycetes and aspergillus
a
Bacterial mixture and trichoderma viride
Actinomycetes and aspergillus
Ventilation frequency more than once per 4 h (n)
178
69
128
146
Frequency of pesticide-use more than five times per quarter of a year (n)
196
73b
102
143
Re-entry interval at least 4 h following a pesticide application (number of farmers)
887
144
237
369
and mild FLD, respectively. There were significantly more men with FLD (66.55 %, 205/308) than women (33.44 %, 103/308) (v2 = 39.93, P \ 0.005; male and female ratio: 2:1). Of the 308 farmers with FLD, 25.32 % (78/308) were also diagnosed with COPD, who were mainly older than 50 years of age. Moreover, 60 (19.48 %, 60/308) were simultaneously diagnosed with asthma, who were mainly middle-aged (30–40 years old) non-smokers. The common clinical manifestations of these farmers with FLD include dizziness, headache, cough, lassitude, fever, chest stuffiness, pain in the neck, loins, and knees, allergic dermatosis, and digestive tract diseases, as listed in Table 3. Besides, comparisons of FLD prevalence in different subgroups are shown in Table 4.
Risk Factors for FLD Among Greenhouse Farmers A logistical regression model was used to evaluate risk factors for FLD. As shown in additional Table 1, the potential risk factors for FLD in greenhouse farmers include years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m2 but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, bathing frequency, not washing up after working in greenhouse, heating fuel items inside the
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Table 2 The characteristics of 5,420 farmers who accepted and answered the questionnaire in full Characteristics
Male (n)
Female (n)
Total (n)
\ 30
212
220
432
30–39 40–49
638 851
662 883
1,300 1,734
50–59
771
800
1,571
[ 60
188
195
383
Smoker
1,374
528
1,902
Non-smoker
1,286
2,232
3,518
Age (years)
Smoking history
Smoking index (packets per year) 0–14.9
1,304
2,256
3,560
15–29.9
521
223
744
[ 30
835
281
1,116
Working period as a greenhouse farmer (years)
per 4 h; [4] 62.99 % (194/308) were in greenhouse with frequency of pesticide-use more than five times per quarter of a year or re-entry interval less than 4 h following a pesticide application; [5] 73.70 % (227/308) were subjects without a respiratory protection when working inside greenhouse; [6] 61.04 % (188/308) were in greenhouses with humidity greater than 65 %; [7] 84.42 % (260/308) were subjects working as a greenhouse for more than 5 years; [8] all the FLD farmers were reported to have had asthma in their childhood or FLD in their family history. Other Symptoms Among Greenhouse Farmers Of 5,420 subjects, 23.54 % (1,276/5,420) exhibited upper respiratory tract infection symptoms and evanescent catarrh symptoms, 19.19 % (1,040/5,420) bronchial asthma, 17.47 % (947/5,420) COPD, 14.39 % (780/5,420) pain in the neck, loins, and knees, 11.73 % (636/5,420) allergic dermatosis, 5.9 % (320/5,420) arthritis or joint abnormalities, 3.69 % (200/5,420) dizziness, 2.21 % (120/5,420) varicose vein, 1.48 % (80/5,420) ocular diseases, and 1.48 % (80/5,420) digestive tract diseases.
\3
372
386
758
4–6
239
248
487
7–9
744
773
1,517
10–19 [ 20
1,143 162
1,187 166
2,330 328
Family working history as greenhouse farmers
1,717
1,806
3,523
Discussion
Personal working history as an employee
943
954
1,897
Allergic history
129
118
247
To our knowledge, this population-based study is the first to evaluate the prevalence of FLD and to explore the potential risk factors for FLD among greenhouse farmers. The major findings to emerge from this study were: (1) nearly 6 % of the greenhouse farmers had FLD caused by workplace environmental system; (2) a number of classic risk factors for FLD among greenhouse farmers were identified, including years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m2 but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, bathing frequency, not washing up after working in greenhouse, heating fuel items inside the greenhouse, microorganism concentration in the near-surface soil of greenhouse, cough in childhood, pneumonia history, frequent access to greenhouse, allergy history, and education background. FLD has been extensively reported in many countries, particularly among diary farmers, indicating a prevalence of 1.3 % in Italy, 1.7 % in Finland, 3.9 % in Wisconsin, USA, 4.9 % in Ireland, 2.3–8.6 % in Scotland, and 8.3–11.4 % in China [8–11]. In the current study, we found a prevalence of nearly 6 % among greenhouse farmers, which was lower than previous report from Jiangsu
greenhouse, microorganism concentration in the near-surface soil of greenhouse, cough in childhood, pneumonia history, frequent access to greenhouse, allergy history, and education background. Of 5,420 subjects, 35.1 % (1,902/5,420) were smokers and among them 72.24 % (1,374/1,902) were male and 27.76 % (528/1,902) were female. Notably, there were significantly more male smokers with FLD (70.09 %, 150/214) than female smokers (29.91 %, 64/214) (v2 = 110.51, P \ 0.05). In the subgroup of working as a greenhouse farmer for more than 5 years, no significant difference of FLD rates was observed between nonsmokers and farmers with smoking index greater than 14.9. However, there were more FLD with severe symptoms in the latter subgroup, suggesting that cigarette smoking may have severe impact on the FLD progression. Furthermore, the majority of subjects diagnosed with FLD were in the following subgroups: [1] 63.96 % (197/308) were in greenhouses with height less than 1.8 m; [2] 82.47 % (254/ 308) were in greenhouses with areas greater than 30 m2 but without a ventilation facility; [3] 65.91 % (203/308) were in greenhouse with ventilation frequencies less than once
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Cell Biochem Biophys (2015) 71:1051–1057 Table 3 The common clinical manifestations of 308 farmers with FLD
Greenhouse variables
Vegetable cultivation (n/ %)
Poultry farming (n/ %)
Mushroom cultivation (n/ %)
Flower cultivation (n/ %)
Total
Total subjects
2,168 (40)
813 (15)
1,084 (20)
1,355 (25)
5,420 (100 %)
Farmers with FLD
FLD farmer’s lung disease
1055
102 (33.11)
45 (14.61)
77 (25)
84 (27.27)
308 (5.7)
Fever
80 (44.44)
20 (11.11)
38 (21.11)
42 (23.33)
180 (58.44)
Cough
14 (7.29)
48 (25)
92 (47.92)
38 (19.79)
192 (62.34)
Chest stuffiness
66 (41.25)
13 (8.13)
43 (26.88)
38 (23.75)
160 (51.95)
Dizziness or headache
17 (42.5)
9 (22.5)
Lassitude or weight loss
31 (26.72)
12 (10.34)
40 (34.48)
33 (28.45)
116 (37.66)
Lung crackling sounds/rales bilaterally
44 (26.83)
26 (15.85)
48 (29.27)
46 (28.05)
164 (53.25)
Imaging changes
36 (23.53)
34 (22.22)
43 (28.10)
40 (26.14)
153 (49.67)
Lung function abnormalities Increasing of acidocyte
35 (23.81)
32 (21.77)
41 (27.89)
39 (26.53)
147 (47.73)
12 (41.38)
4 (13.79)
6 (20.69)
7 (24.14)
29 (9.42)
Positive of serum antibody
51 (37.5)
17 (12.5)
36 (26.47)
32 (23.52)
136 (44.16)
Arthritis or joint abnormalities Ocular diseases
42 (36.21)
14 (12.07)
27 (23.28)
33 (28.45)
116 (37.66)
5 (20.83)
7 (29.17)
8 (33.33)
4 (16.67)
24 (7.79)
Allergic dermatosis
18 (18.75)
32 (33.33)
27 (28.13)
19 (19.79)
96 (31.17)
Pain in the neck, loins, or knees
52 (30.77)
14 (8.28)
46 (27.220
57 (33.73)
169 (54.87)
8 (20)
6 (15)
40 (12.99)
Varicose vein
23 (62.16)
4 (10.81)
3 (8.11)
7 (18.92)
37 (12.01)
Digestive tract diseases
19 (59.38)
2 (6.25)
6 (18.75)
5 (15.63)
32 (10.39)
Province (a southern province of China). This difference may largely result from the farming methods used in the studied population, because of active and exclusive greenhouse farmers enrolled in the present study. Furthermore, geographical factors, diagnostic methods, individual (age, gender, and smoking status), and occupational characteristics of the studied population may also contribute to the differences of FLD prevalence among different regions [4]. Therefore, large-scale population-based studies need to be performed to further estimate the FLD prevalence among Chinese farmers. Because HP and specific antibodies are more frequent in non-smokers, extensive studies were therefore performed to demonstrate the hypothesis that cigarette smoking may protect from HP. It is now well recognized that cigarette smoking exerts a protective role in the prevention of HP [12–14]. In consistent with these findings, no significant difference of FLD (the most common form of occupational HP) prevalence was observed between smokers and nonsmokers in our study (v2 = 2.9979, P [ 0.05), but smokers with FLD were associated with delayed disease progression
and severe symptoms. Marie-Rene’e and colleagues found that smoking habits affect alveolar macrophage phagocytosis and decrease their capacity to produce interleukin 1 (IL-1) and tumor necrosis factor (TNF). In addition, nicotine is able to inhibit immunological processes in the lungs and decreases total bronchoalveolar lavage (BAL) cells like lymphocytes [14]. These observations would partly explain the protective role for cigarette smoking in the prevention of HP. Additionally, Israel-Assayag E et al. reported that blockade of CD28/B7 interactions by CTLA4-Ig inhibits SR-induced lung inflammation and immune response to SR Ag in mice, which may be an additional mechanism undying the protective role of cigarette smoking in the prevention of HP [15]. The European Farmers’ Study reported 3.2 % asthma prevalence for crop farmers and E Monso et al. found an occupational 7.7 % asthma prevalence in greenhouse flower and/or ornamental plant growers [16–18]. Surprisingly, the present study showed an unexpectedly high 19.19 % prevalence of occupational asthma for our studied population. We speculate that this high prevalence is not
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Table 4 Comparisons of FLD prevalence in different subgroups Characteristics
Total
Prevalence (%)
Farmers with FLD (n)
Percent (%)
Total
5,420
5.7
308
100
2,660 2,760
7.71 3.73
205 103
66.55 33.44
\ 30
432
2.78
12
3.90
30–39
1,300
4.69
61
19.81
40–49
1,734
5.94
103
33.44
50–59
1,571
7.26
114
37.01
[ 60
383
4.70
18
5.84
Smoker
1,902
4.94
94
30.52
Non-smoker
351
6.08
214
69.48
Gender Male Female Age (years)
Smoking history
examine the bacterial endotoxin and dust concentrations in the air inside greenhouses and fails to determine whether or not these factors were associated with the prevalence of FLD. Our research team is interested in identifying more triggers of FLD related to greenhouse farming in our future studies. In conclusion, this study suggests an estimation of 5.7 % prevalence of FLD in a larger population of greenhouse farmers in the Northeastern China. Considering the total of greenhouse farmers, we surmise that FLD is and will continue to be a real health problem for Chinese farmers. Fortunately, FLD is preventable, controllable, and treatable. The results of our study also suggest a number of potential risk factors, which may provide ways to reduce exposure and allow individuals to return to their farming activities. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers will be greatly reduced.
Smoking index (packets per year) 0–14.9
3,560
6.21
214
71.75
15–29.9
744
7.73
221
18.18
[ 30
1,116
2.78
56
10.06
Working period as a greenhouse farmer (years) 1 758 2.77 21
6.82
3–5
487
5.54
27
8.77
[5
4,175
6.23
260
84.42
Greenhouse variables Vegetables cultivation
2,168
4.70
102
33.11
Poultry farming
813
5.54
45
14.61
Mushroom cultivation
1,084
7.10
77
25
Flower cultivation
1,355
6.20
84
27.27
\ 1.8 m
3,396
5.80
197
63.96
[ 1.8 m
2,024
5.48
111
36.04
Ventilation frequency less than once per 4 h
3,397
5.98
203
65.91
Frequency of pesticideuse more than five times per quarter of a year
1,656
8.64
143
46.43
Re-entry interval less than 4 h following a pesticide application
1,637
9.29
152
49.35
Greenhouse height
only attributable to occupational asthma related to sensitization present as contaminants in the air of the greenhouse, but also the difference in the farming methods between China and European countries. In addition, the FLD farmers in our study were mainly associated with restrictive ventilatory disorder and lung diffusion dysfunction. Bacterial endotoxin is known to be the occupational causative factor for lung inflammation and lung function injury [19–21]. However, the current study did not
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Acknowledgments This work was supported by Grants from the National Science & Technology Pillar Program of China during the Eleventh Five-year Plan Period (No. 2007BAI24B04), the Project of Department of Science and Technology, Liaoning Province (No. 20132253030), and the Project of Shenyang Science and Technology Bureau (No. F12-277-1-71).
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ORIGINAL PAPER
Prevalence and Risk Factors for Farmer’s Lung in Greenhouse Farmers: An Epidemiological Study of 5,880 Farmers from Northeast China Shuo Liu • Donghong Chen • Shuang Fu • Yangang Ren • Lingling Wang • Yibing Zhang Mingjing Zhao • Xiaoyu He • Xiaoge Wang
•
Published online: 26 October 2014 Ó Springer Science+Business Media New York 2014
Abstract The objectives of this epidemiological study were to evaluate the prevalence of farmer’s lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse,
ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m2 but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced. Keywords Farmer’s lung disease Greenhouse Prevalence
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s12013-014-0308-7) contains supplementary material, which is available to authorized users. S. Liu D. Chen L. Wang M. Zhao X. He X. Wang (&) Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, 4 East Chongshan Road, Shenyang 110032, Liaoning, People’s Republic of China e-mail: [email protected] S. Fu Department of Respiratory Medicine, The General Hospital of Fushun Mining Affairs Bureau, Fushun 113008, Liaoning, People’s Republic of China Y. Ren The Editorial Office, Chinese Journal of Practical Internal Medicine, Shenyang 110001, Liaoning, People’s Republic of China Y. Zhang Department of Scientific Research, The General Hospital of Shenyang Military Command, Shenyang 110015, Liaoning, People’s Republic of China
Farmer’s lung disease (FLD), the most prevalent form of occupational hypersensitivity pneumonitis (HP), is an important source of respiratory morbidity among farmers caused by chronic inhalation of microorganisms from moldy hay, straw, or grain [1]. These microorganisms are mainly composed of Thermophilic actinomyces, such as Saccharopolyspora rectivirgula (SR) or Thermoactinomyces vulgaris (TV) that grow in hay under the conditions of high temperature and high humidity [2, 3]. Clinically, FLD is generally characterized by influenza-like and respiratory symptoms, including dyspnea, cough, lassitude, headaches, nausea, occasional fever, and night sweating [4, 5]. It is estimated that the prevalence of FLD in farming populations range from 0.5 to 4.4 %, depending on various regions, climate, and seasons as well as differences in diagnostic methods and farming practices [1, 4]. In particular, FLD has been reported to be more common in the Northern latitudes and among diary farmers [1].
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China is still an agricultural country with approximately 360 million farmers consisting half of its labor force. To our knowledge, however, epidemiological studies have seldom been performed in Chinese farmers to evaluate the prevalence of FLD or to explore the potential risk factors for FLD. Plastic film greenhouse is a horticultural and agricultural facility with efficient energy conservation that provides the owner with an opportunity to grow plants year-round in a controlled environment. Over the years, due to demand of off-season vegetables and export of cut flowers, plastic film greenhouse has gained its popularity in Middle and North China since 1980 s. In recent years, more and more greenhouse farmers were diagnosed with FLD in our clinical practice. Therefore, this prompts us to conduct an epidemiological study to estimate the prevalence and to explore the potential risk factors for FLD among Chinese greenhouse farmers, which may provide insight into exposures associated with FLD, as well as ways to reduce exposure and allow individuals to return to their farming activities. To this end, we performed a screening survey between August 2006 and June 2009 on FLD in active and exclusive greenhouse farmers in four different regions of Liaoning Province.
Methods Plastic Film Greenhouses and Subjects A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of the four cities of Liaoning Province (Shenyang, Xinmin, Chaoyang, and Jinzhou). The characteristics of these greenhouses were measured and summarized in Table 1, including the height, inside temperature, relative humidity, ventilation frequency, sunlight duration, pesticide usage as well as the temperature, relative humidity, pH value and microorganisms of both surface and near-surface soil (10 cm layer). Farmers meeting any of the following criteria were excluded: (a) prior chronic respiratory diseases when working as a greenhouse farmer, such as chronic bronchitis, tuberculosis, bronchiectasis, bronchial asthma, intrathoracic sarcoidosis, or interstitial lung disease; (b) prior allergy-driven lung disease or organic dust toxic syndrome when working as a greenhouse farmer; (c) any one refuses or is not considered safe to undergo pulmonary ventilation function test such as with mental disorder, severe cardiovascular and cerebrovascular diseases, or surgical operation in the preceding 12 months; (d) refuses to answer the questionnaire or answers the items less than one-third of the questionnaire; (e) unable to measure the
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characteristics of the greenhouses. Out of the 5,880 invited subjects, 5,420 gave their informed consent and answered the questionnaire in full (response rate, 92.18 %); consisting of 2,660 men (2,660/5,420, 49.08 %) and 2,720 women (2,760/5,420, 50.92 %) with a mean age of 44.76 ± 10.66 years (range 22–74 years). The detailed characteristics of these farmers are shown in Table 2. The current study was approved by the regional ethics committee. Questionnaire A questionnaire with 99 items on age, gender, smoking habits, medical history, respiratory symptoms, and occupation details was used. All the questionnaires were filled out by several well-trained respiratory physicians through face-to-face interactions with the subjects. Measurements The pulmonary ventilation function of all participants was measured using a REF 910520 spirotel (Roma, Italy). Approximately 10–15 % of greenhouse farmers with FLD symptoms and 5 % of healthy farmers were asked to undergo additional clinical evaluations, including blood routine examination, blood gas analysis, sputum eosinophil count, routine chest X-ray, and measurement of serum precipitating antibody. The diagnosis of chronic obstructive pulmonary disease (COPD) and asthma was based on the conventional diagnostic criteria as previously described [6, 7]. Statistical Analysis All data were analyzed using the SPSS 11.5 statistical software package (SPSS, Inc., Chicago, IL, USA). Comparisons of prevalence rates were assessed by v2 test. The risk factors were evaluated by odds ratios and 95 % confidence interval (95 % CI) with a logistic regression model. A P value equal to or less than 0.05 was reported as statistically significant.
Results Prevalence of FLD in Greenhouse Farmers Out of the 5,880 invited subjects, 5,420 gave their informed consent and answered the questionnaire in full (response rate, 92.18 %). Of these 5,420 greenhouse farmers, 5.7 % (308/5,420) were diagnosed with FLD. According to the criteria described in Methods, 62.34 % (192/308) and 37.66 % (116/308) of them were further defined as severe
Cell Biochem Biophys (2015) 71:1051–1057 Table 1 Greenhouse characteristics
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Greenhouse variables
Vegetable cultivation
Poultry farming
Mushroom cultivation
Flower cultivation
Total (n)
334
126
167
208
\ 1.8 m
65
40
138
179
[ 1.8 m
269
86
29
29
Spring
28
14
23
15
Winter
28
23
24
22
Autumn
23
15
23
13
Spring
68
67
83
67
Winter Autumn
67 65
68 67
82 83
66 63
Spring
27
15
22
14
Winter
26
23
23
20
Autumn
23
14
20
12
11
12
11
11
Height (n)
Inside air temperature (°C)
Inside humidity (%)
Temperature of surface soil (°C)
Sunlight duration per day (h) Spring Winter
8
12
8
8
Autumn
10
12
10
11
Near-surface soil
a
The near-surface soil in poultry farming greenhouse is not available because of cement mortar protective course
b
Disinfectant, but not pesticide, is used in poultry farming greenhouse
Temperature (°C)
17
a
18
15
Humidity (%)
74
a
80
70
pH value
7.1
a
7.3
6.8
Microorganisms
Actinomycetes and aspergillus
a
Bacterial mixture and trichoderma viride
Actinomycetes and aspergillus
Ventilation frequency more than once per 4 h (n)
178
69
128
146
Frequency of pesticide-use more than five times per quarter of a year (n)
196
73b
102
143
Re-entry interval at least 4 h following a pesticide application (number of farmers)
887
144
237
369
and mild FLD, respectively. There were significantly more men with FLD (66.55 %, 205/308) than women (33.44 %, 103/308) (v2 = 39.93, P \ 0.005; male and female ratio: 2:1). Of the 308 farmers with FLD, 25.32 % (78/308) were also diagnosed with COPD, who were mainly older than 50 years of age. Moreover, 60 (19.48 %, 60/308) were simultaneously diagnosed with asthma, who were mainly middle-aged (30–40 years old) non-smokers. The common clinical manifestations of these farmers with FLD include dizziness, headache, cough, lassitude, fever, chest stuffiness, pain in the neck, loins, and knees, allergic dermatosis, and digestive tract diseases, as listed in Table 3. Besides, comparisons of FLD prevalence in different subgroups are shown in Table 4.
Risk Factors for FLD Among Greenhouse Farmers A logistical regression model was used to evaluate risk factors for FLD. As shown in additional Table 1, the potential risk factors for FLD in greenhouse farmers include years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m2 but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, bathing frequency, not washing up after working in greenhouse, heating fuel items inside the
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Table 2 The characteristics of 5,420 farmers who accepted and answered the questionnaire in full Characteristics
Male (n)
Female (n)
Total (n)
\ 30
212
220
432
30–39 40–49
638 851
662 883
1,300 1,734
50–59
771
800
1,571
[ 60
188
195
383
Smoker
1,374
528
1,902
Non-smoker
1,286
2,232
3,518
Age (years)
Smoking history
Smoking index (packets per year) 0–14.9
1,304
2,256
3,560
15–29.9
521
223
744
[ 30
835
281
1,116
Working period as a greenhouse farmer (years)
per 4 h; [4] 62.99 % (194/308) were in greenhouse with frequency of pesticide-use more than five times per quarter of a year or re-entry interval less than 4 h following a pesticide application; [5] 73.70 % (227/308) were subjects without a respiratory protection when working inside greenhouse; [6] 61.04 % (188/308) were in greenhouses with humidity greater than 65 %; [7] 84.42 % (260/308) were subjects working as a greenhouse for more than 5 years; [8] all the FLD farmers were reported to have had asthma in their childhood or FLD in their family history. Other Symptoms Among Greenhouse Farmers Of 5,420 subjects, 23.54 % (1,276/5,420) exhibited upper respiratory tract infection symptoms and evanescent catarrh symptoms, 19.19 % (1,040/5,420) bronchial asthma, 17.47 % (947/5,420) COPD, 14.39 % (780/5,420) pain in the neck, loins, and knees, 11.73 % (636/5,420) allergic dermatosis, 5.9 % (320/5,420) arthritis or joint abnormalities, 3.69 % (200/5,420) dizziness, 2.21 % (120/5,420) varicose vein, 1.48 % (80/5,420) ocular diseases, and 1.48 % (80/5,420) digestive tract diseases.
\3
372
386
758
4–6
239
248
487
7–9
744
773
1,517
10–19 [ 20
1,143 162
1,187 166
2,330 328
Family working history as greenhouse farmers
1,717
1,806
3,523
Discussion
Personal working history as an employee
943
954
1,897
Allergic history
129
118
247
To our knowledge, this population-based study is the first to evaluate the prevalence of FLD and to explore the potential risk factors for FLD among greenhouse farmers. The major findings to emerge from this study were: (1) nearly 6 % of the greenhouse farmers had FLD caused by workplace environmental system; (2) a number of classic risk factors for FLD among greenhouse farmers were identified, including years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m2 but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, bathing frequency, not washing up after working in greenhouse, heating fuel items inside the greenhouse, microorganism concentration in the near-surface soil of greenhouse, cough in childhood, pneumonia history, frequent access to greenhouse, allergy history, and education background. FLD has been extensively reported in many countries, particularly among diary farmers, indicating a prevalence of 1.3 % in Italy, 1.7 % in Finland, 3.9 % in Wisconsin, USA, 4.9 % in Ireland, 2.3–8.6 % in Scotland, and 8.3–11.4 % in China [8–11]. In the current study, we found a prevalence of nearly 6 % among greenhouse farmers, which was lower than previous report from Jiangsu
greenhouse, microorganism concentration in the near-surface soil of greenhouse, cough in childhood, pneumonia history, frequent access to greenhouse, allergy history, and education background. Of 5,420 subjects, 35.1 % (1,902/5,420) were smokers and among them 72.24 % (1,374/1,902) were male and 27.76 % (528/1,902) were female. Notably, there were significantly more male smokers with FLD (70.09 %, 150/214) than female smokers (29.91 %, 64/214) (v2 = 110.51, P \ 0.05). In the subgroup of working as a greenhouse farmer for more than 5 years, no significant difference of FLD rates was observed between nonsmokers and farmers with smoking index greater than 14.9. However, there were more FLD with severe symptoms in the latter subgroup, suggesting that cigarette smoking may have severe impact on the FLD progression. Furthermore, the majority of subjects diagnosed with FLD were in the following subgroups: [1] 63.96 % (197/308) were in greenhouses with height less than 1.8 m; [2] 82.47 % (254/ 308) were in greenhouses with areas greater than 30 m2 but without a ventilation facility; [3] 65.91 % (203/308) were in greenhouse with ventilation frequencies less than once
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Cell Biochem Biophys (2015) 71:1051–1057 Table 3 The common clinical manifestations of 308 farmers with FLD
Greenhouse variables
Vegetable cultivation (n/ %)
Poultry farming (n/ %)
Mushroom cultivation (n/ %)
Flower cultivation (n/ %)
Total
Total subjects
2,168 (40)
813 (15)
1,084 (20)
1,355 (25)
5,420 (100 %)
Farmers with FLD
FLD farmer’s lung disease
1055
102 (33.11)
45 (14.61)
77 (25)
84 (27.27)
308 (5.7)
Fever
80 (44.44)
20 (11.11)
38 (21.11)
42 (23.33)
180 (58.44)
Cough
14 (7.29)
48 (25)
92 (47.92)
38 (19.79)
192 (62.34)
Chest stuffiness
66 (41.25)
13 (8.13)
43 (26.88)
38 (23.75)
160 (51.95)
Dizziness or headache
17 (42.5)
9 (22.5)
Lassitude or weight loss
31 (26.72)
12 (10.34)
40 (34.48)
33 (28.45)
116 (37.66)
Lung crackling sounds/rales bilaterally
44 (26.83)
26 (15.85)
48 (29.27)
46 (28.05)
164 (53.25)
Imaging changes
36 (23.53)
34 (22.22)
43 (28.10)
40 (26.14)
153 (49.67)
Lung function abnormalities Increasing of acidocyte
35 (23.81)
32 (21.77)
41 (27.89)
39 (26.53)
147 (47.73)
12 (41.38)
4 (13.79)
6 (20.69)
7 (24.14)
29 (9.42)
Positive of serum antibody
51 (37.5)
17 (12.5)
36 (26.47)
32 (23.52)
136 (44.16)
Arthritis or joint abnormalities Ocular diseases
42 (36.21)
14 (12.07)
27 (23.28)
33 (28.45)
116 (37.66)
5 (20.83)
7 (29.17)
8 (33.33)
4 (16.67)
24 (7.79)
Allergic dermatosis
18 (18.75)
32 (33.33)
27 (28.13)
19 (19.79)
96 (31.17)
Pain in the neck, loins, or knees
52 (30.77)
14 (8.28)
46 (27.220
57 (33.73)
169 (54.87)
8 (20)
6 (15)
40 (12.99)
Varicose vein
23 (62.16)
4 (10.81)
3 (8.11)
7 (18.92)
37 (12.01)
Digestive tract diseases
19 (59.38)
2 (6.25)
6 (18.75)
5 (15.63)
32 (10.39)
Province (a southern province of China). This difference may largely result from the farming methods used in the studied population, because of active and exclusive greenhouse farmers enrolled in the present study. Furthermore, geographical factors, diagnostic methods, individual (age, gender, and smoking status), and occupational characteristics of the studied population may also contribute to the differences of FLD prevalence among different regions [4]. Therefore, large-scale population-based studies need to be performed to further estimate the FLD prevalence among Chinese farmers. Because HP and specific antibodies are more frequent in non-smokers, extensive studies were therefore performed to demonstrate the hypothesis that cigarette smoking may protect from HP. It is now well recognized that cigarette smoking exerts a protective role in the prevention of HP [12–14]. In consistent with these findings, no significant difference of FLD (the most common form of occupational HP) prevalence was observed between smokers and nonsmokers in our study (v2 = 2.9979, P [ 0.05), but smokers with FLD were associated with delayed disease progression
and severe symptoms. Marie-Rene’e and colleagues found that smoking habits affect alveolar macrophage phagocytosis and decrease their capacity to produce interleukin 1 (IL-1) and tumor necrosis factor (TNF). In addition, nicotine is able to inhibit immunological processes in the lungs and decreases total bronchoalveolar lavage (BAL) cells like lymphocytes [14]. These observations would partly explain the protective role for cigarette smoking in the prevention of HP. Additionally, Israel-Assayag E et al. reported that blockade of CD28/B7 interactions by CTLA4-Ig inhibits SR-induced lung inflammation and immune response to SR Ag in mice, which may be an additional mechanism undying the protective role of cigarette smoking in the prevention of HP [15]. The European Farmers’ Study reported 3.2 % asthma prevalence for crop farmers and E Monso et al. found an occupational 7.7 % asthma prevalence in greenhouse flower and/or ornamental plant growers [16–18]. Surprisingly, the present study showed an unexpectedly high 19.19 % prevalence of occupational asthma for our studied population. We speculate that this high prevalence is not
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Table 4 Comparisons of FLD prevalence in different subgroups Characteristics
Total
Prevalence (%)
Farmers with FLD (n)
Percent (%)
Total
5,420
5.7
308
100
2,660 2,760
7.71 3.73
205 103
66.55 33.44
\ 30
432
2.78
12
3.90
30–39
1,300
4.69
61
19.81
40–49
1,734
5.94
103
33.44
50–59
1,571
7.26
114
37.01
[ 60
383
4.70
18
5.84
Smoker
1,902
4.94
94
30.52
Non-smoker
351
6.08
214
69.48
Gender Male Female Age (years)
Smoking history
examine the bacterial endotoxin and dust concentrations in the air inside greenhouses and fails to determine whether or not these factors were associated with the prevalence of FLD. Our research team is interested in identifying more triggers of FLD related to greenhouse farming in our future studies. In conclusion, this study suggests an estimation of 5.7 % prevalence of FLD in a larger population of greenhouse farmers in the Northeastern China. Considering the total of greenhouse farmers, we surmise that FLD is and will continue to be a real health problem for Chinese farmers. Fortunately, FLD is preventable, controllable, and treatable. The results of our study also suggest a number of potential risk factors, which may provide ways to reduce exposure and allow individuals to return to their farming activities. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers will be greatly reduced.
Smoking index (packets per year) 0–14.9
3,560
6.21
214
71.75
15–29.9
744
7.73
221
18.18
[ 30
1,116
2.78
56
10.06
Working period as a greenhouse farmer (years) 1 758 2.77 21
6.82
3–5
487
5.54
27
8.77
[5
4,175
6.23
260
84.42
Greenhouse variables Vegetables cultivation
2,168
4.70
102
33.11
Poultry farming
813
5.54
45
14.61
Mushroom cultivation
1,084
7.10
77
25
Flower cultivation
1,355
6.20
84
27.27
\ 1.8 m
3,396
5.80
197
63.96
[ 1.8 m
2,024
5.48
111
36.04
Ventilation frequency less than once per 4 h
3,397
5.98
203
65.91
Frequency of pesticideuse more than five times per quarter of a year
1,656
8.64
143
46.43
Re-entry interval less than 4 h following a pesticide application
1,637
9.29
152
49.35
Greenhouse height
only attributable to occupational asthma related to sensitization present as contaminants in the air of the greenhouse, but also the difference in the farming methods between China and European countries. In addition, the FLD farmers in our study were mainly associated with restrictive ventilatory disorder and lung diffusion dysfunction. Bacterial endotoxin is known to be the occupational causative factor for lung inflammation and lung function injury [19–21]. However, the current study did not
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Acknowledgments This work was supported by Grants from the National Science & Technology Pillar Program of China during the Eleventh Five-year Plan Period (No. 2007BAI24B04), the Project of Department of Science and Technology, Liaoning Province (No. 20132253030), and the Project of Shenyang Science and Technology Bureau (No. F12-277-1-71).
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